有氧运动增加APP+PS1转基因小鼠皮层突触数目、降低Aβ和cofilin异常聚集

Aerobic Exercise Increases Synaptic Loss,Attenuates Aggregation of Aβand Cofilin in the Cortex of APP / PS1 Transgenic Mice

目的:探讨有氧运动对6月龄APP+PS1双转基因小鼠皮层Aβ沉积及突触cofilin异常聚集的影响。方法:清洁级APP+PS1小鼠随机分为安静组(AS)、运动组(AE),同月龄C57BL/6J小鼠为正常对照组(CS)。AE组进行8周跑台运动,5 d/周,60 min/d。前10 min运动速度15 m/min,后50 min运动速度18 m/min,跑台坡度为0°。跳台回避实验和旋转杆平衡实验检测行为学变化,记录小鼠错误反应次数、达标率及不同转速下运动时间。免疫组化和免疫荧光方法检测额叶和颞叶Aβ、突触素(Synapsin,Syn)表达。Western blot检测额叶和颞叶cofilin、Syn的表达。透射电镜观察cofilin-rod结构。结果:1)行为学:6月龄APP+PS1小鼠较CS组错误次数显著升高(P<0.05),达标率降低(P<0.05),相同转速下运动时间显著减少(P<0.01);8周有氧运动显著降低其错误次数(P<0.05),使达标率有所增加,并使平衡能力得到改善。2)6月龄APP+PS1小鼠额叶和颞叶均出现Aβ沉积、cofilin的异常聚集(以额叶更明显),同时Syn表达较CS组显著减少(额叶减少更显著,P<0.01)。电镜下额叶、颞叶轴突均出现微丝微管排列紊乱,有聚集形成棒状结构的倾向,可见早期空泡变性。3)有氧运动明显减少6月龄APP+PS1小鼠皮层Aβ的沉积、使额叶异常聚集的cofilin显著减少(P<0.01),同时增加了突触前Syn含量。电镜下可见轴浆内微丝微管排列整齐,结构趋于正常。结论:有氧运动抑制6月龄APP+PS1转基因小鼠皮层Aβ沉积,减少cofilin的异常聚集,从而增加突触前Syn含量,是其提高行为学能力的机制之一。

Objective： This study aimed to investigate the effect of aerobic exercise on the extent of amyloid （Aβ） deposits and cofilin aggregation in the cortex of APP/PS1 transgenic mice. Methods： APP/PS1 transgenie mice （4 months old） were randomly divided into 8 weeks exercise group （AE） and sedentary group （Aβ） respectively, and C57BL/6J mice （4 months old） were taken as the control group （CS）. The AE group＇ mice were underwent treadmill at 15m/rain （the first 10 min） or 18rn/min （the following 50 rain） for 60 rain, 0- slope, 5 d/week, for 8 weeks. After exercise, the behavioral change was detected by step-down fear conditioning and rotarod test, and the wrong response number, pass rate and exercise time at different rotated speed were recorded. The expressions of Aβ, synapsin （Syn） in frontal and temporal lobe were tested by Immunofluorescenee and Immunohistochemis- try, the expressions of eofilin and Syn in frontal and temporal lobe were detected by Western blotting, and the cofi- lin-rod structure was observed by transmission electron microscopy （SEM）. Results ： 1 ） Behaviorally, compared with CS group, mice of AS group had more wrong movements, lower pass rate, and less exercise time at the same rotated speed （ Ps 〈 0.05） , but mice of AE group had less wrong movements, higher pass rate and better balance ability （Ps 〈 0.05）. 2） There was aggregation of Aβ and cofilin in frontal and temporal lobe in AS group mice, and the Syn expression in AS group was higher than that in CS group （ P 〈 0.05 ） , especially in frontal lobe. ASgroup mice＇s microtubules and microfilaments of axon were disordered, they were going to be aggregated, and vac- uolar degeneration was observed. 3 ） AE group mice had less aggregation of Aβ, less abnormal aggregation of cofi- lin （P 〈0.01 ） , higher Syn level. Their microtubules and microfilaments were ordered and had normal structure. Conclusion： Aerobic exercise may reduce the extent of A- deposition in cortex and inhibit cofilin aggregation and synaptic loss in APP/PS1 transgenic mice, which is one mechanism for exercise improving the ability of behavior.